Microbes are ubiquitous and we as humans come into constant contact with an enormous diversity of microbes. Microbes that interact with humans and cause disease/illness are termed pathogens. Other microbes, e.g. the human gut microbiota, have evolved to form symbiotic relationships with humans and positively impact human health or even human behavior in many different ways.
Established in Nov. 2015, the Lab of Antibody Structure is keen to understand the complex interplay between the host and diverse types of microbes. Embracing a variety of interdisciplinary techniques (Figure 1) and mutually beneficial collaborations, we currently focus our research on serval high-risk infectious diseases and their causative microbes, including coronavirus (CoVs), human immunodeficiency viruses (HIV) and Plasmodium. Through unraveling the interplay between host and these microbes at molecular level, we are devoted to uncover novel drug targets against the infection of these pathogens and related drug candidates discovery. Our long-term goal is to understand and modulate the functions of important host receptors and pathogenic effectors for the prevention, diagnosis and treatment of various microbial infection.
Figure 1. The lab utilizes an ‘integrative structural biology’ approach. The lab expertise embraces not only canonic structural biology means (x-ray, EM and SAXS), but also structural proteomics approaches (CL-MS, HDX-MS and proteomics) and bioinformatics (MD simulation, homology model building) tools.
Since Nov. 2015, we have gradually established ourselves along the research directions mentioned above. For instance, in a work from our lab, we were able to identify novels sites of therapeutic vulnerabilities in Enterovirus (unpublished and not shown). In another study, together with our collaborators at Fudan University, we developed a pan-coronavirus (pan-CoV) fusion inhibitor EK1 (Figure 2). EK1 targets the HR1 domains of various human coronavirus (HCoV) spike (S) proteins to prevent the host-HCoV membrane fusion process and inhibit the host entry of HCoVs into the target cells. The same study also demonstrates for the first time that the HR1 region of coronavirus (CoV) S protein is indeed a druggable and conserved target for pan-CoV fusion inhibitors, thereby providing theoretical basis and framework for future development of broad-spectrum anti-HCoV drugs (Xia et al, 2019, Science Advances).
Figure 2. The potent and broad-spectrum antiviral activity of EK1. a. Broad-spectrum inhibitory activity of EK1 against pseudotyped CoVs infection; b. The antiviral mechanism of EK1 peptide.